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Allogeneic ABCB5-positive Stem Cells for Treatment of CVU

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03257098
Recruitment Status : Recruiting
First Posted : August 22, 2017
Last Update Posted : February 19, 2020
Sponsor:
Collaborators:
FGK Clinical Research GmbH
Ticeba GmbH
Granzer Regulatory Consulting & Services
Information provided by (Responsible Party):
RHEACELL GmbH & Co. KG

Tracking Information
First Submitted Date  ICMJE August 17, 2017
First Posted Date  ICMJE August 22, 2017
Last Update Posted Date February 19, 2020
Actual Study Start Date  ICMJE November 16, 2017
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 19, 2018)
  • Percentage of wound size reduction [ Time Frame: Week 12 post baseline, or last available post-baseline measurement if the Week 12 measurement is missing ]
    Percentage of wound size reduction at Week 12, or last available post-baseline measurement of Weeks 6, 8 or 10 if the Week 12 measurement is missing (last observation carried forward [LOCF]).
  • Assessment of adverse event (AE) occurrence [ Time Frame: Up to 12 months ]
    All AEs occurring during the clinical trial will be registered, documented and evaluated.
Original Primary Outcome Measures  ICMJE
 (submitted: August 17, 2017)
  • Percentage of wound size reduction [ Time Frame: Week 12 post baseline, or last available post-baseline measurement if the Week 12 measurement is missing ]
    Percentage of wound size reduction at Week 12, or last available post-baseline measurement of Weeks 6, 8 or 10 if the Week 12 measurement is missing (last observation carried forward [LOCF]).
  • Assessment of adverse event (AE) occurrence [ Time Frame: During all patient visits except screening ]
    All AEs occurring during the clinical trial will be registered, documented and evaluated.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 19, 2018)
  • Percentage of wound size reduction [ Time Frame: Weeks 2, 3, 4, 6, 6.1, 6.2, 8, 10, and 12 (without LOCF); ]
  • Absolute wound size reduction [ Time Frame: Weeks 2, 3, 4, 6, 6.1, 6.2, 8, 10, and 12 ]
  • Proportion of patients achieving complete wound closure [ Time Frame: Weeks 2, 3, 4, 6, 8, 10, 12, and at any time point ]
  • Time to first complete wound closure [ Time Frame: A priori specification not possible; between baseline and week 12 post baseline ]
  • Proportion of patients achieving 30% wound closure [ Time Frame: Weeks 2, 3, 4, 6, 6.1, 6.2, 8, 10, 12, and at any time point ]
  • Time to first 30% wound closure [ Time Frame: A priori specification not possible; between baseline and week 12 post baseline ]
  • Epithelialization [ Time Frame: Weeks 2, 3, 4, 6, 6.1, 6.2, 8, 10, and 12 ]
  • Assessment of further wound healing parameters: formation of granulation tissue and wound exudation [ Time Frame: Visit 3 and Visit 10 before IMP application, Days 1 to 3 and 8, Weeks 2, 3, 4, 6, 6.2, 8, 10, and 12 ]
  • Pain assessment as per numerical rating scale (NRS) [ Time Frame: Days 0, 1 to 3 and 8, Weeks 2, 3, 4, 6, 6.1, 6.2, 8, 10, and 12 ]
  • Assessment of quality of life (QoL) using the short form 36 (SF-36) questionnaire [ Time Frame: Day 0 and Weeks 4, 8 and 12 ]
  • Assessment of dermatology-specific quality of life based on the Dermatology Life Quality Index (DLQI) questionnaire [ Time Frame: Day 0 and Weeks 4, 8 and 12 ]
  • Physical examination and vital signs at Week 6.1 and Week 12 [ Time Frame: Week 6.1 and Week 12 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: August 17, 2017)
  • Percentage of wound size reduction [ Time Frame: Weeks 2, 3, 4, 6, 8, 10, and 12 (without LOCF); ]
  • Absolute wound size reduction [ Time Frame: Weeks 2, 3, 4, 6, 8, 10, and 12 ]
  • Proportion of patients achieving complete wound closure [ Time Frame: Weeks 2, 3, 4, 6, 8, 10, 12, and at any time point ]
  • Time to first complete wound closure [ Time Frame: A priori specification not possible; between baseline and week 12 post baseline ]
  • Proportion of patients achieving 30% wound closure [ Time Frame: Weeks 2, 3, 4, 6, 8, 10, 12, and at any time point ]
  • Time to first 30% wound closure [ Time Frame: A priori specification not possible; between baseline and week 12 post baseline ]
  • Epithelialization [ Time Frame: Weeks 2, 3, 4, 6, 8, 10, and 12 ]
  • Assessment of further wound healing parameters: formation of granulation tissue and wound exudation [ Time Frame: Day 0 before IMP application, Days 1 and 8, Weeks 2, 3, 4, 6, 8, 10, and 12 ]
  • Pain assessment as per numerical rating scale (NRS) [ Time Frame: Days 0, 1 and 8, Weeks 2, 3, 4, 6, 8, 10, and 12 ]
  • Assessment of quality of life (QoL) using the short form 36 (SF-36) questionnaire [ Time Frame: Day 0 and Weeks 4, 8 and 12 ]
  • Assessment of dermatology-specific quality of life based on the Dermatology Life Quality Index (DLQI) questionnaire [ Time Frame: Day 0 and Weeks 4, 8 and 12 ]
  • Physical examination and vital signs at Week 12 [ Time Frame: Week 12 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Allogeneic ABCB5-positive Stem Cells for Treatment of CVU
Official Title  ICMJE An Interventional, Single Arm, Multicenter, Phase I/IIa Clinical Trial to Investigate the Efficacy and Safety of Allo-APZ2-CVU on Wound Healing of Chronic Venous Ulcer (CVU)
Brief Summary The aim of this clinical trial is to investigate the efficacy (by monitoring the wound size reduction of Chronic Venous Ulcers) and safety (by monitoring adverse events) of the medicinal product to be studied after two applications on the wound surface in patients with Chronic Venous Ulcers.
Detailed Description

This is an interventional, single arm, phase I/IIa clinical trial to investigate the efficacy and safety of allogeneic ABCB5-positive mesenchymal stem cells (MSCs) on wound healing in patients with chronic venous ulcer (CVU). Allogeneic MSCs will be isolated ex vivo and will be expanded in vitro. The IMP incorporating the ABCB5-positive MSCs will then be applied on the wound surface of CVU under local anesthesia (on Day 0 and Week 6.1).

Wound measurements from Visit (V) 2 and V9 will be used to determine the cell amount for the IMP treatments on V3 and V10, respectively.

Patients are followed up for efficacy for 3 months which allows to distinguish actual wound healing from transient wound coverage.

The wound healing process will be documented by standardized photography. The wound size evaluation will start on the day of the first change of wound dressing. The quality of the wound healing process will be assessed on the basis of formation of granulation tissue, epithelialization and wound exudation.

Pain will be assessed using a numerical rating scale and quality of life will be investigated with standardized and validated questionnaires. To assess long-term safety of allo-APZ2-CVU three follow-up visits at Months 6, 9 and 12 after the first IMP applications are included.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Intervention Model Description:
Interventional, single arm, multicenter, phase I/IIa clinical trial
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Skin Ulcer Venous Stasis Chronic
Intervention  ICMJE Biological: allo-APZ2-CVU
Suspension of ABCB5-positive mesenchymal stem cells
Study Arms  ICMJE Experimental: allo-APZ2-CVU
Application of IMP on patients wound
Intervention: Biological: allo-APZ2-CVU
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 17, 2017)
37
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2021
Estimated Primary Completion Date June 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female patients aged 35 to 85 years;
  2. Chronic venous leg ulcer (as defined by the current AWMF guidelines: therapy resistant ulcer that shows no improvement within 3 months despite of optimal phlebological therapies or is not healed within 12 months) diagnosed by doppler ultrasonography (DUS), ankle brachial index (ABI, 0.9-1.3), physical examination and dermatological review;
  3. Wound size of target ulcer between 1.5 and 100 cm2 measured by a standardized photography at the screening visits (Visit 1 and Visit 2);
  4. Wound location below knee;
  5. If patients are suffering from 2 or more ulcers at the same extremity, the target ulcer has to be separated by a minimum bridge of 1 cm of epithelialized skin from other ulcers (the largest ulcer should be the target ulcer, if not decided otherwise at discretion of the investigator; the target ulcer is defined at Visit 1);
  6. Body mass index (BMI) between 20 and 45 kg/m²;
  7. Patients understand the nature of the procedure and are providing written informed consent prior to any clinical trial procedure;
  8. Women of childbearing potential must have a negative blood pregnancy test at Visit 1
  9. Women of childbearing potential and their partner must be willing to use highly effective contraceptive methods during the course of the clinical trial.

Exclusion Criteria:

  1. Evidence of the ulcer extending to the underlying muscle, tendon, or bone;
  2. Current use of systemic steroid medication above Cushing threshold dose (>7.5 mg/d prednisone or equivalent);
  3. Diabetes mellitus that has to be evaluated by blood test (Haemoglobin A1c [HbA1c] >7.5%);
  4. Peripheral Artery Disease (PAD) including claudication with need of treatment;
  5. Acute deep vein thrombosis (maximum 30 days from diagnosis) or a still untreated deep vein thrombosis;
  6. Unable to tolerate leg ulcer compression bandage;
  7. Infection of the target ulcer requiring treatment as judged clinically;
  8. Any chronic dermatological disorders diagnosed at the investigator's discretion;
  9. Skin disorders, unrelated to the ulcer, that are present adjacent to the target wound;
  10. Current use of medications that influence wound healing: systemic immunosuppressives, cytotoxic medicinal products, and systemic steroids (above Cushing-threshold level);
  11. Known abuse of alcohol, drugs, or medicinal products;
  12. Cancerous or pre-cancerous lesions adjacent to the target wound;
  13. Patients anticipated to be unwilling or unable to comply with the requirements of the protocol;
  14. Pregnant or lactating women;
  15. Systemic infectious disease diagnosed by serology testing human immunodeficiency virus (HIV˗1, HIV-2);
  16. Any known allergies to components of the IMP;
  17. Prior surgical procedures such as bypass or mesh-graft treatment within 2 months prior to Visit 1;
  18. Patients with significant ulcer healing or wound size enlargement of more than 25% at Visit 2 compared to Visit 1;
  19. Treatment of target ulcer with active wound care agents (e.g. iruxol, local antibiotics or silver dressings), which have not been paused 14 days before IMP application;
  20. Current or previous (within 30 days of enrollment) treatment with another IMP, or participation and/or under follow-up in another clinical trial;
  21. Previous participation in this clinical trial (except for screening failures due to an inclusion or exclusion criterion);
  22. Evidence of any other medical conditions (such as psychiatric illness, physical examination, or laboratory findings) that may interfere with the planned treatment, affect the patient's compliance, or place the patient at high risk of complications related to the treatment;
  23. Employees of the sponsor, or employees or relatives of the investigator.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 35 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Christoph Ganss, Dr. +49 6221 71833 ext 0 office@rheacell.com
Contact: Kathrin Dieter 49 6221 71833 ext 0 kathrin.dieter@rheacell.com
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03257098
Other Study ID Numbers  ICMJE allo-APZ2-CVU-II-01
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party RHEACELL GmbH & Co. KG
Study Sponsor  ICMJE RHEACELL GmbH & Co. KG
Collaborators  ICMJE
  • FGK Clinical Research GmbH
  • Ticeba GmbH
  • Granzer Regulatory Consulting & Services
Investigators  ICMJE
Principal Investigator: Andreas Kerstan, Dr. Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Würzburg
PRS Account RHEACELL GmbH & Co. KG
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP